Good day, and thank you for standing by. Welcome to the Sangamo Therapeutics fourth quarter and full year 2021 conference call. At this time, all participants are in listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during this session, you'll need to press star, then one on your telephone keypad. Please be advised today's conference may be recorded. If you require operator assistance during the call, please press star, then zero. I'd now like to hand the conference over to your host today, Aron Feingold, Head of Corporate Communications. Please go ahead. Good afternoon, and thank you for joining us today. With me this afternoon on this call are several members of the Sangamo executive leadership team, including Sandy MacRae, Chief Executive Officer, Mark McClung, Chief Operating Officer, Prathyusha Duraibabu, Chief Financial Officer, Jason Fontenot, Chief Scientific Officer, Rob Schott, Head of Development, and Bettina Cockroft, Chief Medical Officer. Slides from our corporate presentation can be found on our website, sangamo.com, under the Investors and Media section, Events and Presentations page. This call includes forward-looking statements regarding Sangamo's current expectations. These statements include, but are not limited to, statements relating to the therapeutic and commercial potential of our product candidates, the anticipated plans and timelines of Sangamo and our collaborators for initiating and conducting clinical trials and presenting clinical data, execution of our corporate strategy, advancement of our product candidates, our initial 2022 financial guidance, and other statements that are not historical facts. Actual results may differ materially from what we discuss today. These statements are subject to certain risks and uncertainties that are discussed in our filings with the SEC, specifically our annual report on Form 10-K for the fiscal year ended December 31st, 2021. The forward-looking statements stated today are made as of this date, and we undertake no duty to update such information except as required by law. On this call, we discuss our non-GAAP operating expenses. Reconciliation of this measure to our GAAP operating expenses can be found in today's press release, which is available on our website. Now I'd like to turn the call over to our CEO, Sandy Macrae. Thanks, Aron, and good afternoon to everybody on the call. I'd like to start by saying that 2021 was a significant year for Sangamo as we continue to advance the development of genomic medicines for patients across multiple therapeutic areas using our innovative technologies. We are very pleased with our progress despite the challenges of the second year of the pandemic. We are advancing potentially transformative genomic medicines in the clinic and strategically using our R&D capabilities to pursue indications of unmet need. These efforts are supported by our manufacturing infrastructure, including in-house AAV and cell therapy facilities. Our collaboration partners also help us drive towards our mission to deliver on the promise of genomic medicine, and we believe that this progress positions us as well to generate long-term value for our shareholders. In 2021, we have executed upon our strategy with several important achievements. First, we and our partners advanced our three lead programs while presenting compelling clinical data. Starting with our wholly owned phase I/II Fabry disease program, we presented updated data at the WORLDSymposium earlier this month. We are encouraged by the safety and efficacy data we have seen to date, and most importantly, the patients in the study have reported they are feeling better. Investigators are observing improvements in some of the most challenging symptoms, including ability to sweat in the first three treated patients. With the recent changes in the Fabry competitive landscape, we believe we are in a leading position. In the second half of this year, we plan to present additional updated phase I/II data. We're actively planning for a phase III study, including discussions with health authorities, patient advocacy groups, and investigators. We are also delighted by the emerging phase I/II sickle cell disease data presented at ASH in December, showing no treatment-related adverse events in the four treated patients, improvement across several biomarkers, and most importantly, clinically significant reduction in painful sickling crisis. We anticipate that the next four patients treated in the study will be dosed with a product candidate manufactured using improved methods that have been shown in the internal experiments to increase long-term progenitor cells. We expect to complete dosing of these patients in the third quarter of this year. Transition planning of the program from Sanofi to Sangamo is going well, and we are energized to have this asset back in our hands soon as we assess the best way to move the program forward for patients, be that on our own or with a potential partner. Finally, we are encouraged by the follow-up data presented at ASH last year from our Hemophilia A program partnered with Pfizer. Updated phase I/II results show sustained bleeding control in the highest dose cohort through two years following gene therapy. Regarding the phase III study, Pfizer has announced that it hopes to obtain agreements with the health authorities to resume their AFFINE trial in the first half of 2022. The trial was previously paused when some of the patients experienced factor VIII activity greater than 150% following treatment. Pfizer is currently in the process of submitting a protocol amendment to health authorities in the countries where this trial is being conducted and preparing responses to the FDA clinical hold. Over 50% of the patients have been enrolled in the phase III AFFINE trial. Second, we're progressing our preclinical candidates based on our second-generation technologies, CAR-T reg for autoimmune disease and zinc finger transcription factors for neurological disorders. We have enrolled and expect to dose soon the first patient in our lead CAR- T reg program, where we are evaluating TX200 for the prevention of immune-mediated rejection in HLA-A2 mismatched kidney transplant from a living donor. We believe that this will be the first patient ever to be dosed with a CAR- T reg therapy, and that we are in a leading position with several companies following us into this very promising area. We believe that our expertise across multiple technology platforms, robust cell therapy infrastructure, supported by our manufacturing facilities and genomic engineering capabilities and internal strategic and operational synergies comprise a differentiated CAR- T reg platform from which we can potentially offer patients advanced genomic medicines. In addition to our proof of concept study of TX200, we are progressing our preclinical allogeneic renal transplant rejection study, as well as inflammatory bowel disorder and multiple sclerosis programs, including presenting the first preclinical data from our allogeneic IL-23R CAR-Treg candidate in IBD last year. Finally, with regard to our zinc finger protein transcription factor technology in treating CNS disorders, in addition to our partner programs with Biogen, Novartis, Takeda and Pfizer, we are advancing multiple internal programs. Third, we continue to hone our differentiated genome engineering platform, including improving the specificity, precision, and efficiency of our core zinc finger proteins. We're also progressing our capabilities from nucleases to repressors, activators, and even base editors, and are excited about our progress. We see Sangamo's capabilities as representing a one-stop shop for a range of genomic engineering capabilities that are designed to be applied therapeutically. Fourth, we continue to work diligently with our collaborators, supporting the advancement of our partner programs in the clinic while driving research efforts for preclinical programs for which we receive reimbursement from our partners. These partnerships have been a key component of our development strategy and continue to drive value for Sangamo. We believe that the buy-in from pharma validates our mechanistic approach across a range of advanced modalities and as it enables us to benefit substantially from our partners' domain expertise to develop high-quality therapeutics for patients. The capital provided by our partnerships helps to advance our internal pipeline of assets while providing our partner programs with the resources needed to advance the development of these potentially transformative therapies more quickly. Fifth, we completed and brought online our cell therapy manufacturing facilities in Brisbane and Valbonne and now have operational AAV and cell therapy facilities in-house. We believe these facilities provide many strategic advantages, including flexibility and control, capacity to support our R&D needs, process expertise, geographic diversification, and that supports supply chain resilience and a deep intellectual property portfolio. Six, we believe that we have a strong financial position to take us through our key upcoming catalysts. Our diverse and accomplished leadership team and our talented employees are passionate about our mission and have enabled our multiple 2021 accomplishments, setting us up for what we expect to be a strong 2022. I am very grateful to my leadership team and all my Sangamo colleagues for their dedication and hard work in a second challenging year of the pandemic. With that, I'd like to turn the call over to our Head of Development, Rob Schott, who will discuss the data from our clinical programs in more detail. Thanks, Sandy, and good afternoon to everyone on the call. We are delighted by our clinical execution in 2021. We believe the presentation last year of important proof of concept data supports late-stage development for our Fabry and sickle cell programs. At the WORLDSymposium earlier this month, we presented updated preliminary results from the phase I/II STAAR clinical study evaluating isaralgagene civaparvovec or ST-920, a wholly owned gene therapy candidate for the treatment of Fabry disease. As of the November 9th, 2021 cut-off date, the gene therapy candidate continued to be generally well-tolerated across three dose cohorts in the five treated patients with treatment-related adverse events that were assessed as grade one or mild. Elevated alpha-Gal A activity has been maintained for the four patients treated in the first two dose cohorts, ranging from threefold to fifteenfold above mean normal at last measurement. For the two patients on enzyme replacement therapy, alpha-Gal A activity measured at ERT trough was 15-fold above mean normal at week 52 for the patient in cohort one and 10-fold above mean normal at week 25 for the patients in cohort two. For the two ERT pseudo-naïve patients, alpha-Gal A activity was three-fold above mean normal at week 52 for the patient in cohort one and four-fold above mean normal at week 40 for the patients in cohort two. The two patients in cohort one have now begun the long-term follow-up study, and at the one-year mark, alpha-Gal A expression remains robust. Withdrawal from ERT has been completed for one patient and is planned for the second patient on enzyme replacement therapy based on the stability of their alpha-Gal A activity following treatment. For the first patient in cohort three, alpha-Gal A activity has increased into the mean normal range at week two. As Sandy noted, three of the patients have reported clinical improvement with a greater ability to sweat. This allows for greater exercise tolerance in active individuals. The cardiac magnetic resonance imaging data suggests stabilization of important MRI parameters in two patients. This will be followed at intervals to confirm the cardiac benefits of therapy. One patient with a significant elevation in plasma lyso-Gb3 pretreatment showed a significant reduction from baseline of approximately 40% in this biomarker after treatment with ST-920 within 10 weeks after dosing and maintained through week 36. Patients with lower baseline levels of lyso-Gb3 maintained steady levels through the cutoff date. The sixth patient in the study, who is the second patient in cohort three, was recently dosed after the cutoff date. We expect to provide updated results from the STAAR study in the second half of 2022 and are currently planning for a phase III clinical trial. At ASH 2021, we announced updated preliminary proof of concept data from the phase I/II PRECIZN-1 study of SAR445136 for the treatment of sickle cell disease. As of the September 22nd, 2021 cutoff date, the most recently treated patient in the study has been followed for 26 weeks, and the longest treated patient had been followed for 91 weeks. In all four treated patients, there were increases in total hemoglobin, fetal hemoglobin, and percent F cells. None required blood transfusion to post-engraftment. The SAR445136 investigational drug product had on-target BCL11A gene modification of between 61%-78% in all four patients. There were no adverse events related to therapy with SAR445136. One patient had a single sickle cell crisis or vaso-occlusive crisis nine months after treatment. There have been no additional serious adverse events reported. Additional data from this study are expected to be presented at a medical meeting in 2022, and dosing of patients in this study is expected to be completed by the third quarter of 2022. We are currently collaborating with Sanofi on planning for a transfer of its responsibilities under this program back to Sangamo this June. We look forward to keeping you apprised with future updates regarding these exciting clinical studies. With that, I'll turn it over to Prathyusha for a financial update. Prathyusha? Thank you, Rob, and good afternoon. Our financial results for the fourth quarter and the full year are available in the press release we issued and can also be found on our website. I want to reiterate that 2021 was a significant year for Sangamo, with execution on many fronts as we continue to progress the advancement of our lead programs, our preclinical research pipeline, and our in-house manufacturing capabilities. With approximately $465 million in cash equivalents, and marketable securities at the end of the year, we believe that our balance sheet remains strong for continued execution across our platforms and programs. Turning to our initial 2022 full year guidance, we expect non-GAAP operating expenses to be between $280 million-$310 million for the year. This range excludes estimated non-cash stock-based compensation expense of approximately $40 million. We expect a significant portion of our operating expenses to be invested in continued progress of our lead programs, including Fabry phase III planning activities, phase I/II activities for TX200, and preclinical work in CAR-Treg and CNS indications. We also expect to grow our investment in sickle cell in the second half of the year following the transfer of the program back to Sangamo. I will now turn the call back to Sandy for closing remarks. Thank you, Prathyusha. We are excited by where we stand as a company and believe we have a bright future. We are a fully integrated genomic medicine company building momentum with our novel science, clinical execution, and in-house manufacturing. In 2022, we look forward to providing expected updates on phase I/II Fabry data, selection of a dose for cohort expansion, and phase III planning. Dosing of patients in the CAR-Treg STEADFAST trial. Phase I/II sickle cell data and dosing of patients in the PRECIZN-1 study and the transition of the program from Sanofi to Sangamo. Pfizer's progress with the pivotal phase III hemophilia A trial. We will now turn it over to the operator to open the line for questions. If you'd like to ask a question at this time please press the star then the number one key on your touchtone telephone. To withdraw your question press the pound key. Our first question comes from Nicole Germino with Truist Securities. Good afternoon, everyone, and thank you for taking my question and congrats on all the progress. If I could ask a two-part question. The first one is, in the backdrop of other companies experiencing clinical holds with their gene therapy programs, can you address the safety concerns that integration risks around your vector for hem A and for ST-920 for Fabry? And second, for your CAR-Treg platform, how necessary is it for a kill switch for regulatory agencies? Or maybe put another way, what gives you confidence that you don't need one? Thank you for your question. If I could address the first one, and then I'll pass the second one on to Rob. Safety is really important to us, and that's why we look on safety as the primary endpoint of all of the studies that we've done with our AAV6 vector. We've been really pleased by the safety throughout all of the programs, the MPS programs, hemophilia A, and now with Fabry disease. We're gathering an increasing body of data that convinces us that this form of delivery is safe for the patients that we serve. Now, the choice of diseases remains important because we always have to balance benefit and risk. We spend a long time thoughtfully gathering preclinical data, sharing it with the regulators, starting at doses that allow us to be sure that patient safety is maximally protected, and then sharing with the community any concerns we have as the trial progresses. I'm delighted with our progress so far. I think it's unfortunate when others have run into difficulties because it does cloud the whole field. It's the advantage of us having a vector that we've worked with and have gathered a lot of safety data. Rob, can you answer the second one? Yes. I'd like some clarification on the kill switch and what you're suggesting that we program that into the cell therapy so that we can turn off the T regs. Is that the- Yes. [crosstalk] That's the question. Yeah. Yeah. Cause a couple of your competitors have you know a kill switch. Is it necessary for regulatory agencies? You know, have regulatory agencies had any input on this? If not, like, is it? Do you need a kill switch, or what gives you confidence that you don't need one? Yeah, we've not been asked to engineer in a kill switch. Again, these are T regulatory cells that we're engineering for these programs. They are responsible for inhibiting the immunologic response and rejection in the case of renal transplants. It's a different proposition than engineering other types of T cells, killer T cells or CD8 T cells. I'd actually like to ask Jason to comment on that too. Jason, can you help us with some thoughts on this? Yeah. Thanks, Sandy and Rob. Yeah, I think what I can say is that we're very confident about the approach that we're using in the TX200 program. We've evaluated the safety and the efficacy of the cells in a variety of preclinical models, and we've been very happy with what we've seen. We've obviously consulted with our own internal experts, clinical, regulatory, safety, and we've had conversations with the regulators and we're moving forward, and we're excited to be dosing our first patient in this quarter. You know, other companies take different approaches, but we're confident that our approach is one that is going to offer a benefit for patients, and we'll be keeping a close eye on patients as they're treated. Obviously, this is a phase I study where safety is paramount, and that's what our focus is on. Thank you, Jason. Thanks so much. Our next question comes from Yanan Zhu with Wells Fargo. Hi. Thanks for taking my questions. First on Fabry program. You mentioned you will have additional data in the second half of the year. I was just wondering what might be the follow-up, and presumably this is going to include all six patients. The question is the length of the follow-up and in terms of the endpoints. I think we can assume ERT withdrawal is an important endpoint, enzyme level substrate, but would there be any additional clinical endpoints that's also going to be studied at that to be reported at that stage? Thanks. Thank you for your question. This is about the longer-term data on Fabry and what we'll be able to show. Bettina, you've been following this trial very closely. Yes, thank you so much for the question. Later on this year, we will have accumulated more data, especially from the earlier dose patients. As you may know, the parent study, these patients have been enrolled into as a one-year study, and patients that have been treated at the beginning. Some of these patients have now rolled over to the long-term follow-up study, which is an additional four years of follow-up in total. We will be able to present data on accumulation of the alpha-Gal A expression over time, as well as other biomarkers like the Gb3 and you point out the ERT withdrawal data. In terms of clinical endpoints, we will be collecting once we dose naïve patients moving forward, we will be collecting kidney biopsy data. This will not be available this year at this later update. We can expect that type of clinical data to be presented next year. We will also be presenting an update on patient-reported outcomes as we move along, we are also intending to dose more patients, and we have patients currently in screening and in baseline, so patients are going to be dosed, we anticipate. It'll give us a wealth of data. Exactly, some that will be a nice profile that we will be collecting from this wealth of data though. What we like from the data we've seen so far is up until the one-year mark that we have concrete data from, there's been no sense of decline in the four patients that have been treated for the longest. That the alpha-Gal A remains elevated, that the lyso-Gb3 remains flat, that the patients remain still get a claim of benefit, talk about symptoms like sweating, talk about their investigators talk about stabilization of the cardiac MRI. Those are all really encouraging data that it's only through time that we'll be able to understand it. However, I want to be absolutely clear, we are full on in our planning for the phase III study and look forward to initiating that as the data from the current study matures. Thank you, and looking forward to hearing about the phase III design. I think maybe it's too early to ask that question. I might, if I may, I'm curious about what you mentioned about base editing programs that you're working on. Obviously this is going to be based on zinc fingers. My question is, does your base editor retain the nuclease part of the zinc finger nuclease, or does it forego that nuclease part? The reason I'm asking is because I think in the CRISPR-based base editors, actually the nickase capability, i.e., the ability to cut one strand of the double-stranded DNA is actually very useful in terms of improving the editing efficiency, because it prevents the degradation of the edited strand. In that light, I'm interested in whether, you know, your architecture for your base editor, basically. Thanks. Thank you for a very interesting question. We've been working on base editors for some time and I'll get Jason to comment in a minute. What gives us great pleasure is that the zinc finger platform allows a range of technologies to be added to the DNA localizing zinc finger and allows us to choose when double-strand breaks with a nuclease are important or whether things like repression, enhancement or base editors are the right things for the right patient, compared to CRISPR, where there's a company for each of these. Jason, can you comment on this specific question, please? Sure. Thank you, Sandy. You know, this is a base editor that will not create double-strand breaks to change a base in the genome. We're really excited about the advancements that we made, and we look forward to sharing them very soon at the appropriate scientific conference. I don't think I'm gonna go into the details of the architecture of the base editor that we've designed, but it's a novel approach and we're very excited about discussing it and deploying it therapeutically. Great. Thanks for the color. The reason we particularly like it is it uses a zinc finger architecture that we've had years of experience with, and so understand about how to tune and how to increase the specificity. It benefits from the small size of zinc fingers and which are, you know, almost a 10th the size of some of the CRISPR architectures, and therefore allow it to be packaged in AAV in a way that the standard base editor won't. It allows us choice, and that's what we like, and that's what our partners like. Got it. Yeah. Thanks. Thanks for highlighting that advantage. Yeah, that's a question in my mind as well. Thank you very much for all the color. Thank you. Our next question comes from Maury Raycroft with Jefferies. Hi. Thank you for taking my question. This is Jing, Maury's line. Actually I have two questions. The first one is, can you talk more about where you are at with this design, designing a Fabry phase III, and what are the gating factors to get all these, you know, these studies being started? That's my first question. Second one is, what else can you talk about the first patients enrolled in the CAR-Treg program? And can you also say if this patient has already been transplanted and are you currently processing the CAR-Tregs? That's my question. Thanks. Let me take the easier one, which is Fabry. Then, Mark, can you just talk about where we are with CAR-Treg in general, please? We haven't shared anything about the phase III study. Mm-hmm. As I'm sure you know, planning for a phase III takes a long time, and therefore, we've been looking at the design of this and talking to experts for at least six months and are pleased with the progress we're making, and we'll share it more broadly at the right time. Mark, can you talk about the T regs because we're very excited by them. Yeah. We're you know about to dose the first patient with our TX200 candidate, and we're very excited about that. As we've talked about, we'll be expecting to dose two patients by the end of the second half of 2022. You know, we're delighted to take this forward because it'll be the first opportunity for us to really establish the biologic effect of these agents and really understand what's going on. This is critical because our goal is that TX200 establishes the foundation for a portfolio of CAR- T regs for major autoimmune indications. This will inform us you know using the autologous. In the meantime, we're advancing allogeneic approaches, and as we've disclosed, we've got, you know, preclinical candidates against MOG in multiple sclerosis as well as IL-23R for inflammatory bowel disease. We'll be applying the learnings that we have coming out of this trial as we advance the platform, but also those particular candidates. Okay, great. Thank you. Thank you very much. Our next question comes from Luca Issi with RBC Capital. Oh, great. Thanks so much for taking my question. Congrats on all the progress. Two quick ones. Maybe the first on Fabry. I will not ask you the design of the phase III, but maybe at high level, can you just talk about what gives you confidence that you can start a phase III here without actually having seen the kidney biopsy data quite yet? Maybe second on sickle cell disease, can you just provide any additional color on the new manufacturing process here? What are some of the key parameters that you're optimizing here that gives you confidence that the new manufacturing process will drive better outcome for patients? Thanks so much. Goodness. Let me see how I can split these. Rob, can you talk about sickle, please? The other question I think you said was in the absence of... If I can just make sure we answer this question correctly. In the absence of kidney biopsy data, which we expect to see in 2023, how will we decide on the go decision and the design of the phase III? As I said, we've been designing this and talking with regulators for some time. We believe that the data, perhaps from AVROBIO, one of our... It used to be one of our competitors, where they showed very small changes in alpha-Gal A beget changes in the renal biopsy data for lyso-Gb3. That in itself gives us confidence that the alpha-Gal A we are seeing should benefit the tissues when we get to that stage. We have to plan in advance, and we have to look at the different doses and the dose-response curve and decide which one we take forward as we accrue data. With respect to the sickle Great. Yeah, go ahead. With respect to the sickle cell program and manufacturing, we have made some process changes. We haven't talked specifically about those process changes, but in internal experiments, we've shown that increases the number of progenitor cells. We're optimistic that this will carry through into the clinic with better yield. We're being very transparent and I hope realistic to say that we believe these will result in clinical benefit, but until we do the clinical experiment, we can't have a direct correlation. That's why we too are very interested in seeing the data from these next three or four patients that will be dosed over the coming months. I want to say, bear testament, say thank you to our friends at Sanofi who are continuing to drive forward the study during the transition period. Got it. Thanks so much. Our next question comes from Ben Burnett with Stifel. Hi. This is Kelly [Greys] on for Ben. Thanks for taking our questions. I just had one quick one about Fabry. Regarding the Fabry program, can you talk at all about the lyso-Gb3 biomarkers, specifically, under what situations would you expect this biomarker to move with the ST-920 treatment? Our second one is about hemophilia, and I was just wondering if Pfizer has already received feedback from the FDA on the necessary steps to remove the clinical hold, or if this is something they have yet to do. Thank you. Bettina, can you do Fabry? Rob, can you do hemophilia, please? Yes, thank you for the question. Lyso-Gb3, you will have seen we presented data on at the WORLDSymposium just a couple of weeks ago in San Diego. Different patients are exhibiting different baseline levels to start off with on lyso-Gb3. The movements that we can expect are going to differ based on this as well. I'd like to point to patient number three, who is the patient, first patient in cohort two, whose lyso-Gb3 started higher than the other patients and for whom we've had a significant more than 40% reduction, and that within the first 10 weeks post-infusion. That reduction has been maintained over time until the latest follow-up. What we look forward to is seeing the next patient, going to be dosing, seeing how their lyso-Gb3 fares over time depending on their baseline. This phenomenon, Bettina, has been seen in all the programs. It's got to be high to go down. It's important to point that out. Thank you, Sandy, because we have seen the same in other programs that the lyso-Gb3 really does need to be at significantly high levels for us to be able to impact it with a gene therapy approach. That has been seen across other programs. We're confident that we're seeing data that is going to be encouraging as we also look at our next patient's dose at the higher dose. Rob, hemophilia. Hemophilia. First, I'd like to acknowledge the terrific partnership with Pfizer on this program and remind everyone that the trial was more than 50% enrolled at the time it was paused. Pfizer has guided us in the markets that the trial will resume or is planning to resume in the first half of 2022. Without getting into the specifics of where we are with responding to regulatory authorities, I can point toward that guidance of resumption of the trial in the first half of this year. It's going very well, and they're putting all their efforts into it. They are aggressively and enthusiastically pursuing this trial. Thank you. Thank you. Our next question comes from Aspen Mori with Bank of America. Hey, guys. Thanks for the question. Maybe you can just talk through your updated thinking as you transition the sickle cell asset over to you guys. Maybe just talk through your updated thinking on how you see that progressing in terms of you know taking it alone or maybe partnering it out. If the priority is partnering, if there's any preference for someone with more of an all-U.S. presence as that was kind of Sanofi's niche as your prior partner. Second question, some of your peers have implied that for the gene therapy space FDA may be stricter on therapies or indications where there's already approved therapies available not including gene therapies. Do you think that's a fair assessment or has that at all been? Have you kind of seen that dynamic play out within your interactions with the FDA? Thank you. I'm gonna ask Mark to talk about our strategy around sickle, and then I'll touch on the general comment for the FDA. Aspen, I mean, obviously we heard, you know, December 30th that they had made that strategic decision to transition sickle cell back to us. As Sandy mentioned, you know, the team's been working very hard on the transition. We're very pleased with the engagement we have with Sanofi as we progress to the transition plan, which will culminate around June 28th of this year. Our highest priority right now is to ensure that we can complete the phase I/II PRECIZN-1 trial, as Rob just mentioned, utilizing that new manufacturing process, which we hope will, you know, come through and demonstrate even better results in those four patients. That totality of that data will inform, you know, kind of the way we want to proceed forward. In the meantime, the teams have engaged the authorities, both in terms of feedback on manufacturing, as well as preliminary discussions around the approach to phase III. At the appropriate time we'll provide an update for that. You know, in terms of the geographies and partnerships, we're not gonna comment on that now. It's too early to provide a perspective on that. I would remind you, right, that in the United States there are about 100,000 sickle cell patients, of which 30,000 of those patients are severe. Outside of the U.S. there's about 150,000 patients. This is a devastating disease that affects a particular population, and our commitment is to do whatever we can to make sure that patients get access to this medicine if it's a differentiated medicine. We'll know more as we get the clinical data. Our commitment is to ensure that we take it forward if it, the data suggests it should get to patients. If I could talk to the more general one about the agency. We have a great relationship with the agency, and I have an enormous respect for Peter and the FDA and what they do, because I think one has to understand the exponential growth in this field that they have to deal with and to train people and to stay ahead of the emerging data and understanding. I think there is a bit of a reality check that we're watching now, which is, more medicines are in the clinic, more new vectors are being tested, and some of them will be found to have challenges, and that's inevitable in any new field. Which takes me back to what I said to one of the earlier questions about our vector having had years of testing in many indications of the team at Sangamo having filed many INDs and understanding the preclinical and toxicology data necessary to ensure safety. And about the inherent belief at Sangamo that it's everything is about the patient and that we put patient safety first and would be the first to have that conversation with the agency if we are ever concerned about what we're seeing. But at the moment, we haven't felt any difference in the agency's approach and are glad to have them as partners in the development of our medicines. Thanks, Sandy. Our next question comes from Ritu Baral with Cowen. Good afternoon, guys. Thanks for taking the question. I had a question on the PRECIZN-1. Well, the sickle cell program in general. You know, I think at a high level, I'd love to know the metrics by which you'll gauge sort of where the program will fit in in a landscape that's getting more and more crowded. You know, to drill down on that, I guess what we're looking for is HbF levels, but also percent F cells. I guess, which one do you think will be more important, a more important tell on the ultimate clinical benefit? especially since you're reaching such high levels of percent F, you know, do you need to show that sort of 90s level of percent F cells in a certain proportion of treated patients for you to say that this is, you know, this is going to be the preferred therapeutic? I'm gonna ask Rob to comment on the technical bit and Mark on more of the strategic. What would remind you that we're in the clinic, we have clinical data. There are many. The competitive landscape is largely of newcomers from other editing modalities putting into the pipeline and talking about doing this. Rob, can you talk about what you'll use as you look for success? What's most important to the patient is the frequency of which they have vaso-occlusive crisis. That is the most important parameter, is relief of those terrible, painful, expensive sickle cell crises. What we have seen in the four patients that we've reported is an enormous effect size. We've had a single VOC, whereas prior to treatment, they were having very frequent vaso-occlusive episodes. If you look at the magnitude of the effect that this therapy has, it's profound. All of the other factors that you mentioned, percent F cells, fetal hemoglobin, are all important. What is most important is the durability of that effect, on and the impact that has on patients' lives. I think with time, we'll understand that relationship between percent F cells and fetal hemoglobin and that protection. We really need to keep our eyes on what's most important to the patients. Nicely said, Rob. Mark, the bigger picture. Just a quick follow-up to that. Do you think that that relationship is well enough understood right now, snapshot in time or will be understood in the next couple of years enough that HbF or some analysis of HbF could be a potential approvable or accelerated approval pivotal endpoint? Will it really come down to VOCs or some other clinical aspect? VOCs are easy to measure. It's not a subtle laboratory-based finding. It's what the patients report. I think that will remain the cornerstone of assessing effective therapies is benefit that provides patients, particularly in this disease. Got it. Mark. Bigger picture. Thank you. Sorry. Thank you. Sorry. Yeah. You know, in terms of that, Ritu, and if I don't answer this, please clarify it for me. Obviously, the CRISPR/Vertex guidance that they're going to file sometime towards the end of this year. You know, they've not shown as much of the dataset yet, at least as far as I know, in terms of any further updates, in particular of the registration-directed study results, which would be expected. You know, time will tell in terms of how the discussions go once they file with the agency. In the meantime, we've also seen Bluebird withdraw. You know, it really becomes important for us to better understand the data that's emerged and we've presented to date. More importantly, as Rob alluded to, the additional four patients with the change in the manufacturing process to see if that has an increased benefit in terms of the HbF levels, percent F cell increases, as well as the clinical outcomes for the patients. I think it's really whether that profile looks competitive enough that will dictate how we take the program forward. Got it. Thanks. Thank you. Our next question comes from Gena Wang with Barclays. Thank you for taking my questions. Two very quick ones. The first one I also follow regarding the sickle cell program. What kind of clinical profile you will be thinking that possible to keep in-house? Would that be CRISPR-like profile, or would that be better? The second question is regarding the base editors. So I assume you use the MNase. What about the IP part? Do you have a proper right to use that? Do you want me to maybe? Yeah. Why don't you talk about sickle, and then Jason can speak to the base editors. Hi, Gena. I hope you're well. In terms of the data that I just sort of alluded to, I think it's really gonna be important to see the clinical profile in these next four patients. It'll give us a sense, you know, roughly around the time that hopefully we'll see a little bit more of an update from CRISPR Vertex, whether we've got a comparable product or whether we've got a differentiated product. At the end of the day, these are personalized cell therapies, which means they need to be manufactured for the patient. As I described, there's, you know, 100,000 of the patients in the U.S., 30,000 of them are severe. Even if there's one competitor in the market, it's gonna take a long time to service the needs of the sickle cell communities, not only in the United States, but more importantly, worldwide. You know, if we've got a attractive profile that's the same or differentiated through CRISPR Vertex, we will do, as I mentioned earlier, what we need to do to either find a partner or look for novel ways that we can get this therapy to patients. Jason, can you help on the base editor question? Sure. Thanks, Sandy. Yeah. You know, regarding the base editor, this is a program that I'm incredibly excited about. We have a great team of molecular biologists, structural biologists that are continually innovating around our core zinc finger platform. They're doing that on both the side of the zinc finger portion of the molecule, where we're refining the specificity and accuracy of the molecules to target specific sequences. They're also doing it on the functionality side, right? You know, moving beyond the core group of functionalities that we already have in our toolkit, nucleases, transcriptional activators, transcriptional re-regulators. We're now exploring other new functionalities, including base editing, but also recombinases and epigenetic editors. You know, we've got something in our base editor program that we're really excited about. We wouldn't be moving forward if we didn't think we had freedom to operate. We're pretty comfortable with the really unique architecture that we've developed. As Sandy pointed out, we think it offers some real advantages in being able to be deployed in a single viral vector, as well as taking advantage of, you know, the great specificity and accuracy aspects of the zinc finger platform. Thank you. Our next question comes from Patrick Trucchio with H.C. Wainwright. Hi. Good afternoon, everyone, and congrats on the progress for this quarter. I just kinda have just two questions. I guess the first one to start off is what are some of the components that can result in the patients having elevated lyso-Gb3 level for Fabry disease? How readily do these patients actually have increased lyso-Gb3? Patrick, can I make sure I understand your question? It's about what Bettina talked about earlier, that many patients, particularly those on ERT, already have reduced lyso-Gb3. There are a few patients, particularly the naïve patients, will have elevated levels, and those are the ones where we can see a benefit of our medicine on the lyso-Gb3. I think like you asked, are we screening for those patients? Is that where you were going? Yes. Yeah. Will you be screening for high lyso-Gb3 patients? We're delighted to take all patients with Fabry, and we take three categories. We take the patients that are on ERT. We take what are called pseudo-naïve, and those are patients that have been on for at least six months. We're not rejecting patients if they have low levels of lyso-Gb3, and we're delighted when we find a patient that's a high level. Okay, great. Kinda just like a follow-up question. Like, for the baseline of, like, for patient five and patient six, do you also see these increases in lyso-Gb3, or is that something that we will see later on? Bettina, have we commented on the levels for patients five and six? Yeah. Thank you for the question. We have not commented on those levels at this point in time. This is something that is part of that update that we can provide later in the year as we provide our clinical update. Okay, great. Thank you for the additional color. I'm showing no further questions in queue at this time. I'd like to turn the call back to Aron Feingold for closing remarks. Thank you all once again for joining us today and for your questions. We look forward to keeping you updated on our future developments. This concludes today's conference call. Thank you for participating. You may now disconnect.